聚乙二醇化 SLN 作为一种有前途的方法，用于将吉非替尼递送至肺癌的淋巴系统。

PEGylated SLN as a Promising Approach for Lymphatic Delivery of Gefitinib to Lung Cancer.

机构信息

Kayyali Chair for Pharmaceutical Industry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

出版信息

Int J Nanomedicine. 2022 Jul 28;17:3287-3311. doi: 10.2147/IJN.S365974. eCollection 2022.

PURPOSE

The present study aimed to develop gefitinib-loaded solid lipid nanoparticles (GEF-SLN), and GEF-loaded PEGylated SLN (GEF-P-SLN) for targeting metastatic lung cancer through the lymphatic system.

METHODS

The prepared SLNs were characterized in terms of physicochemical properties, entrapment efficiency, and in-vitro release. Furthermore, ex-vivo permeability was investigated using the rabbit intestine. Cytotoxicity and apoptotic effects were studied against A549 cell lines as a model for lung cancer.

RESULTS

The present results revealed that the particle size and polydispersity index of the prepared formulations range from 114 to 310 nm and 0.066 to 0.350, respectively, with negative zeta-potential (-14 to -27.6). Additionally, SLN and P-SLN showed remarkable entrapment efficiency above 89% and exhibited sustained-release profiles. The permeability study showed that GEF-SLN and GEF-P-SLN enhanced the permeability of GEF by 1.71 and 2.64-fold, respectively, compared with GEF suspension. Cytotoxicity showed that IC of pure GEF was 3.5 μg/mL, which decreased to 1.95 and 1.8 μg/mL for GEF-SLN and GEF-P-SLN, respectively. Finally, the apoptotic study revealed that GEF-P-SLN decreased the number of living cells from 49.47 to 3.43 when compared with pure GEF.

CONCLUSION

These results concluded that GEF-P-SLN is a promising approach to improving the therapeutic outcomes of GEF in the treatment of metastatic lung cancer.

目的

本研究旨在通过淋巴系统开发用于治疗转移性肺癌的吉非替尼载药固体脂质纳米粒（GEF-SLN）和载药聚乙二醇化固体脂质纳米粒（GEF-P-SLN）。

方法

对制备的 SLN 进行物理化学性质、包封效率和体外释放度的表征。此外，还使用兔肠进行了体外通透性研究。针对肺癌模型 A549 细胞系，研究了细胞毒性和凋亡作用。

结果

结果表明，所制备的制剂的粒径和多分散指数范围分别为 114nm 至 310nm 和 0.066 至 0.350，且具有负的 Zeta 电位（-14 至-27.6mV）。此外，SLN 和 P-SLN 表现出超过 89%的显著包封效率，并表现出持续释放的特征。通透性研究表明，与 GEF 混悬液相比，GEF-SLN 和 GEF-P-SLN 分别使 GEF 的通透性增强了 1.71 倍和 2.64 倍。细胞毒性显示，纯 GEF 的 IC 为 3.5μg/mL，而 GEF-SLN 和 GEF-P-SLN 分别降低至 1.95μg/mL 和 1.8μg/mL。最后，凋亡研究表明，与纯 GEF 相比，GEF-P-SLN 将活细胞数量从 49.47%降低至 3.43%。